Abstract:
:Pandemic outbreaks of influenza are caused by the emergence of a pathogenic and transmissible virus to which the human population is immunologically naïve. Recent outbreaks of highly pathogenic avian influenza (HPAI) of the H5N1 subtype are of particular concern because of the high mortality rate (60% case fatality rate) and novel subtype. In order to develop a vaccine that elicits broadly reactive antibody responses against emerging H5N1 isolates, we utilized a novel antigen design technique termed computationally optimized broadly reactive antigen (COBRA). The COBRA HA sequence was based upon HA amino acid sequences from clade 2 H5N1 human infections and the expressed protein retained the ability to bind the receptor, as well as mediate particle fusion. Non-infectious recombinant VLP vaccines using the COBRA HA were purified from a mammalian expression system. Mice and ferrets vaccinated with COBRA HA H5N1 VLPs had protective levels of HAI antibodies to a representative isolates from each subclade of clade 2. Furthermore, VLP vaccinated animals were completely protected from a lethal challenge of the clade 2.2 H5N1 virus A/Whooper Swan/Mongolia/244/2005. This is the first report describing the use of COBRA-based antigen design. The COBRA HA H5N1 VLP vaccine elicited broadly reactive antibodies and is an effective influenza vaccine against HPAI virus.
journal_name
Vaccinejournal_title
Vaccineauthors
Giles BM,Ross TMdoi
10.1016/j.vaccine.2011.01.100subject
Has Abstractpub_date
2011-04-05 00:00:00pages
3043-54issue
16eissn
0264-410Xissn
1873-2518pii
S0264-410X(11)00172-1journal_volume
29pub_type
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